1. Field of the Invention
The present invention relates to the field of diagnostic assessment of complex biological and physical structures, including bone strength in patients at risk of or suffering from osteoporosis and other conditions that degrade the trabecular structure of cancellous bone. Additional structures include evaluating vasculature in tumors, and hydrocarbon pore distributions in strata.
2. Prior Art
The trabecular architecture is both highly sensitive to metabolic changes in bone (relative to the more dense outer shell of cortical bone) and a major contributor to the overall strength of a bone. Hence it is an appropriate surrogate marker for tracking disease and treatment.
The Impact of Bone Disease Diseases of the skeletal system, including osteoporosis and other less common conditions, are a major threat to the health of the elderly, particularly women. The significance of bone disease is evident from the 2004 Surgeon General's report, “Bone Health and Osteoporosis,” and from the declaration of 2002-2011 as the Decade of the Bone and Joint. More than 10 million Americans over age 50 suffer from osteoporosis (the weakening of the skeletal system as a result of loss of bone mass), and an additional 34 million are at risk. More than 1.5 million fractures occur each year as a result of osteoporosis, with direct costs of care of approximately $15 billion, and billions more in costs associated with loss of productivity and the three-fold increase in risk of mortality associated with fractures. The continuing aging of the population will cause the number of fractures and the associated economic and societal impact to more than double by 2020, with at least 50% of the population over the age of 50 suffering from, or at risk of, osteoporosis.
Diagnosis and Treatment of Osteoporosis The cycle of bone production goes through a number of stages, typically peaking in the early twenties and declining gradually thereafter. In middle age, and particularly in post-menopausal women, the net production of bone can become negative, and the trabecular bone, the structure of rods and plates that supports the outer shell of cortical bone, becomes thinner and weaker. The loss of bone strength that results from the thinned and more porous bone structure in osteoporotic bone increases the risk of fracture in vulnerable regions such as the hip and spine. Although the hip and spine exhibit most of these fractures, they are more difficult to image than the calcaneous (heel bone) and distal radius. Since osteoporosis is a systemic metabolic disease, and the weight-bearing bones are good indicators of the disease state, images of either of these bones are indicative of the progression of the disease in the patient's skeletal system as a whole. The calcaneous is a particularly good bone for assessing trabecular architecture, as it is a weight-bearing bone and relatively accessible for imaging using an MRI (magnetic resonance imager or magnetic resonance imaging).
Osteoporosis is not an inevitable consequence of aging. Proper lifestyle choices, including smoking cessation, moderate exercise, and adequate doses of calcium and vitamin D, can reduce bone loss and fracture risk. Several drugs are also available for the treatment of osteoporosis. Bisphosphonates, including Fosamax™ and Actonel™, are oral agents that reduce the resorption of bone. Teriparatide, marketed under the name Forteo™, is an anabolic hormone extract that stimulates bone growth but must be administered by daily injection. Other forms of hormone therapy also stimulate development of bone but carry significant risk of side effects as shown in recent clinical trials.
Proper therapy requires timely and accurate diagnosis. The current standard in diagnosis of osteoporosis is measurement of bone mineral density (BMD) by dual energy x-ray absorptiometry (DEXA). Recent studies in the USA have indicated that DEXA is underutilized, with less than 25% of the at-risk population receiving BMD testing, due partially to the cost of DEXA but primarily to lack of awareness. Of much greater concern is the fact that physicians have begun to question the clinical relevance of DEXA, based on emerging evidence that DEXA measurements do not properly predict fracture risk and are particularly inadequate in assessing the effectiveness of therapy.
As a result of these concerns, a number of other imaging modalities, including quantitative computed tomography, ultrasound, and magnetic resonance imaging are being explored as alternatives to DEXA. The resistance of bone to fracture depends, as is the case for most materials, not just on density but also on the structure of the bone, including the relative fractions of, and the thickness and orientation of, trabecular rods and plates. MRI, which is inherently a three-dimensional technique, is well suited to the determination of the structural details that determine fracture resistance.
The MRI techniques currently being investigated for diagnosis of osteoporosis require the acquisition of extremely high-resolution images, as well as requiring a number of image processing operations. Images of living bone can be acquired in a high-field MRI system using specialized coils, and lengthy exam times. Careful patient positioning and stabilization are also required. These high-field systems cost around $2 million and need to be housed in carefully controlled environments overseen by radiology specialists. The invention reported here enables devices that can be housed in a typical doctor's office and which cost less than $200,000.
Magnetic Resonance (MR) in some ways is particularly well suited to measuring living bone, as hard-bone (i.e., the calcified structure of the trabeculae and cortical bone) gives very low signal, while marrow (which fills the spaces between the trabecular lattice) gives high signals, hence providing good contrast and good signal to noise. But the high cost of high-field systems, and the need for long acquisition times in order to resolve fine structures combined with the requirement that the patient (imaged body part) not move during acquisition, yield a level of impracticality in the implementation of standard MRI for this purpose.
MRI is based on an extension of the mathematics of Fourier expansion which states that a one-dimensional repetitive waveform (e.g., a signal amplitude as a function of time or an intensity as a function of linear position) can be represented as the sum of a series of decreasing period (increasing frequency) sinusoidal waveforms with appropriate coefficients (k-values).
In MRI, the item (body part) to be imaged is a three-dimensional object. The basic concept of k-values in one dimension can be extended to two or three dimensions. Now, rather than a series of k-values, there is a two or three-dimensional matrix of k-values, each k-value representing a particular spatial frequency and direction in the sample.
In Fourier analysis, converting from the k-values to the desired waveform (amplitude vs. time for a time varying signal or image intensity vs. position for the MRI case) is accomplished by using a Fourier transform. The Fourier transform in simple terms is a well-known means to convert between the frequency domain and time domain (for time varying signals). For images, as in the MRI case, the Fourier transform is used to convert between the spatial-frequency domain (the series of sinusoidal waveforms and their coefficients, referred to as k-space) and the spatial arrangement of signal intensities for each of the imaged volumes (voxels). Similar to the case of time-varying signals, where the k-values are coefficients for the sinusoidal waveforms with given periods, the k-values in the MRI case are the coefficients for the sinusoidal waveforms with given wave lengths (where the wavelengths are inversely related to spatial frequencies, i.e., a long wavelength is a low spatial frequency).
MRI technology today uses a number of methods to acquire images. Virtually all rely on gathering the k-space coefficients and later Fourier transforming them into an image (or set of images as in a 3D acquisition). In the simplest abstraction, this is accomplished by placing the part to be imaged in a strong magnetic field and exciting the hydrogen nuclei in the sample by transmitting at the sample a pulsed radio-frequency electromagnetic signal tuned to the resonant frequency of the hydrogen nuclei. This pulse starts the nuclei resonating at their resonant frequency. Then, to obtain information about where in the sample the signal originates from, the spins of the excited hydrogen atoms are encoded with a combination of phase and frequency encodes corresponding to the desired k-space data being acquired on that excitation. (Here phase and frequency refer to the resonant frequency and phase of the hydrogen nuclei). This is accomplished by modulating the magnetic field spatially and temporally, so as to correspondingly spatially alter the resonant frequency of the nuclei and modulate their phase. A signal is received back then from the excited hydrogen nuclei of the sample, and the k-values are extracted from the signal. This process of excitation, encoding, and signal acquisition is repeated until an entire matrix of k-space values (properly selected to constitute a Fourier series) is acquired with sufficiently high spatial frequency to resolve the desired features in the sample. Finally, the matrix of k-values is Fourier transformed to produce an image or images. There are many variations and extensions of this theme in use in current technology MRI systems. One approach utilizes frequency encoding to localize signals to thin slices and phase encoding to generate the k-values for each of these 2D slices.